Abstract

BACKGROUND: The aim of this study was to evaluate whether –108C/T polymorphism of the paraoxonase 1 (PON1) gene and the plasma enzyme activity are risk factors for adverse cardiac events after coronary artery bypass grafting (CABG).

MATERIAL AND METHODS: Seventy-one patients with coronary heart disease (CHD) undergoing CABG were enrolled in the study. Genomic DNA was extracted from the venous blood using the Gen Elute™ Blood Genomic DNA kit (Sigma) according to the manufacturer’s instructions. PON1 activity was measured in 50 mM glycine/NaOH buffer (pH 10.5) containing 1.0 mM paraoxon, and 1.0mM CaCl2.

RESULTS: The mean PON1 activity toward paraoxon and toward phenyl acetate was equal (166.5±86.9 U/ml and 96.0±47.2 U/ml, respectively) in patients with CHD. The –108C/T polymorphism of PON1 gene was tested. In CABG patients, PON1 activities in dependence on genotypes were significantly different and equalled 266.2±117.9 U/ml for CC, 178.8±64.7 U/ml for CT, and 98.9±59.2 U/ml for TT genotype. Patients with PON1 activity lower than 193.5 U/ml exhibited significantly increased risk of a serious cardiac event in comparison with patients with PON1 activity higher or equal to this value (p=0.03). Additionally, TT genotype was significantly associated with shorter time of event-free survival in comparison with CT and CC genotypes (p=0.009).

CONCLUSIONS: The PON1 polymorphism and enzyme plasma activity are associated with CHD occurrence. High PON1 activity connected with the presence of CC and CT genotypes decreases the recurrence of symptoms of coronary heart disease and improve prognosis after CABG.

Keywords: Coronary Artery Disease, Aryldialkylphosphatase - metabolism, Coronary Artery Bypass - adverse effects, Coronary Disease - genetics, Demography, Kaplan-Meier Estimate, Multivariate Analysis, Polymorphism, Single Nucleotide - genetics, Postoperative Complications - etiology, Prognosis, Promoter Regions, Genetic - genetics